Neural control of breathing

呼吸的神经控制

基本信息

批准号：
10553260
负责人：
JACK L FELDMAN
金额：
$ 78.17万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-11 至 2023-12-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY Breathing is a remarkable behavior fundamental to life that mediates gas exchange to support metabolism and regulate pH. A reliable, non-stop, robust rhythmic pattern of respiratory muscle activity is essential for breathing in mammals. Failure to maintain a normal breathing pattern in humans suffering from sleep apnea, apnea of prematurity, congenital central hypoventilation syndrome, hyperventilation syndrome, Rett syndrome, and perhaps Sudden Infant Death Syndrome, leads to serious adverse health consequences, even death. Various neurodegenerative diseases, such as Parkinson's disease, multiple systems atrophy, and amyotrophic lateral sclerosis, are associated with sleep disordered breathing that we hypothesize results from the loss of neurons in brain areas controlling respiration. If breathing is to be understood in normal and in pathological conditions, the mechanisms for respiratory central pattern generation must be revealed. We focus on two brain sites essential for generation of the normal breathing pattern, the preBötzinger Complex and the retrotrapezoid nucleus/parafacial respiratory group. We propose a broad series of experiments both in vivo and in vitro in rodents using advanced techniques including: viral delivery to express genetically encoded opsins or DREADDs in key subpopulations of neurons in these regions; advanced optical techniques to determine the contributions of the preBötzinger Complex microcircuit to rhythm generation; state-of-the-art neuroanatomical techniques to establish, in appropriate and necessary detail, the interconnectivity of the brainstem respiratory pattern generator. The data from these experiments will provide an extraordinary window into the mechanisms underlying respiratory rhythm and pattern generation.

项目概要呼吸是一种对生命至关重要的非凡行为，它介导气体交换以支持新陈代谢和呼吸肌活动的可靠、不间断、稳健的节律模式对于调节 pH 值至关重要。患有睡眠呼吸暂停的哺乳动物无法维持正常的呼吸模式，早产儿呼吸暂停、先天性中枢性通气不足综合征、通气过度综合征、雷特综合征、也许婴儿猝死综合症会导致严重的不良健康后果，甚至死亡。各种神经退行性疾病，如帕金森病、多系统萎缩、肌萎缩症侧索硬化症与睡眠呼吸障碍有关，我们发现这是由于睡眠呼吸障碍造成的控制呼吸的大脑区域的神经元如果要理解正常和病理状态下的呼吸。在这种情况下，我们必须揭示呼吸中枢模式产生的机制。产生正常呼吸模式所必需的位点：前波辛格复合体和后梯形我们提出了一系列广泛的体内和体外实验。啮齿类动物使用先进技术，包括：病毒传递以表达基因编码的视蛋白或这些区域的关键神经元亚群中的 DREADD 可以确定 preBötzinger Complex 微电路对最先进的神经解剖学的贡献；以适当和必要的细节建立脑干呼吸系统互连性的技术这些实验的数据将为了解该机制提供一个非凡的窗口。潜在的呼吸节律和模式生成。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Monosynaptic Projections to Excitatory and Inhibitory preBötzinger Complex Neurons.

DOI：
10.3389/fnana.2020.00058
发表时间：
2020
期刊：
Frontiers in neuroanatomy
影响因子：
2.9
作者：
Yang CF;Kim EJ;Callaway EM;Feldman JL
通讯作者：
Feldman JL

Silent hypoxaemia in COVID-19 patients.

DOI：
10.1113/jp280769
发表时间：
2021-03
期刊：
The Journal of physiology
影响因子：
0
作者：
Simonson TS;Baker TL;Banzett RB;Bishop T;Dempsey JA;Feldman JL;Guyenet PG;Hodson EJ;Mitchell GS;Moya EA;Nokes BT;Orr JE;Owens RL;Poulin M;Rawling JM;Schmickl CN;Watters JJ;Younes M;Malhotra A
通讯作者：
Malhotra A

Distinct parafacial regions in control of breathing in adult rats.